Identification of low-risk indicators of early stage cervical cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the low-risk indicators of early cervical cancer.</p><p><b>METHODS</b>The medical records of 201 patients undergoing radical surgery between March 2000 and April 2011 for staging Ia2,Ib1 (tumor diameter≤2cm) cervix cancer were retrospectively reviewed, with particular focus on the pathological findings [parametrial involvement, positive margin, positive pelvic lymph node, and lymph vascular space invasion (LVSI)], treatment, and outcomes.</p><p><b>RESULTS</b>The operation duration ranged 75-330min (mean:188.87 min) and the intra-operative blood loss was approximately 100-2500 ml (mean: 583.33 ml). Pathology showed the rate of parametrial spread, positive margins, lymph node metastasis, LVSI was 0, 6.97%, 12.44%, and 17.41%. Based on the pathologic findings, the patients were classified as two groups: group A had 147 patients(73.13%) with no neoplasm or tumor diameter ≤2 cm,while group B had 54 patients (26.87%) with tumor diameter > 2 cm. The incidence of ≥ 1/2 cervical stromal invasion, LVSI, positive lymph node, underlying section of uterus involvement, and low tumor differentiation in group A and B were 20.14% vs. 85.19% (p = 0.000), 13.61% vs. 27.78%(p = 0.019), 9.52% vs. 20.37% (p=0.039), 4.82% vs. 14.81% (p=0.008), and 35.37% vs. 44.44% (p=0.025), respectively, with significant differences. Among the 163 patients who were followed up for more than 3 months, 10(6.13%) developed recurrence whereas no patient died.</p><p><b>CONCLUSIONS</b>Pathologic parametrial involvement in clinical stage 1a2 and 1b1 cervical cancer is uncommon. Tumor size and cervical stromal invasion can be used to identify low-risk population that are worthy of consideration for studies of less radical surgery performed in conjunction with pelvic lymphadenectomy.</p>

Primary sarcoma of the ovary: clinicopathological characteristics, prognostic factors and evaluation of therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The primary ovarian sarcoma is a very rare malignancy. The objective of this study was to further investigate the clinicopathologic features and outcome in patients with primary sarcoma of the ovary.</p><p><b>METHODS</b>Between 1988 and 2007, 24 patients with primary ovarian sarcoma who underwent treatment at Peking Union Medical Hospital were reviewed retrospectively. Response to treatment, progression and overall survival were analyzed.</p><p><b>RESULTS</b>Patients with ovarian sarcoma had a mean age of (54.3 ± 10.3) years, and 16 of them were postmenopausal. The most common symptom was abdominal pain, present in 14 patients. Of the 24 patients, 16 patients were pathologically diagnosed as carcinosarcoma (known as malignant mixed mesodermal tumor (MMMT)), 2 as ovarian leiomyosarcoma (LS) and 6 patients as ovarian endometrial stromal sarcoma (ESS). The patients in optimal debulking group had a median survival period of 28 months and 1-year survival rate of 71%. The patients in suboptimal debulking group had a significantly lower median survival of 6 months (P = 0.02) and 1-year survival rate of 29%. Among the patients, 23 patients received chemotherapy and most of regimens were based on platinum, 3 patients received chemoradiation. The mean number of courses of combined chemotherapy was 6.6 ± 5.0, and the response was unsatisfactory. The median survival for the entire group was 18.7 months. The one-year survival rate was 58%, and two-year survival rate only 29%.</p><p><b>CONCLUSIONS</b>Ovarian primary sarcoma has a poor overall prognosis. Optimal debulking surgery appears to be of prognostic significance. There is a clear need for further study to explore the role and the regimen of platinum-based chemotherapy in primary ovarian sarcoma.</p>

Mullerian adenosarcoma of the uterus: A clinicopathologic analysis of 9 cases / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features, diagnosis, treatment and prognosis of uterine mullerian adenosarcoma.</p><p><b>METHODS</b>The clinicopathological data of 9 cases of uterine mullerian adenosarcoma in PUMC hospital from January 2003 to February 2009 were retrospectively analyzed.</p><p><b>RESULTS</b>There were 6 uterine endometrial adenosarcomas and 3 cervical adenosarcomas. The main clinical manifestations were abnormal vaginal bleeding and pelvic pain. Physical examination showed cervical/vaginal mass, enlarged uterus or pelvic mass. The adenosarcoma was characterized by benign or atypical-appearing neoplastic glands within a sarcomatous stroma. This stroma could appear as periglandular cuffs or intraglandular polypoid projections of increased cellular structure. The primary diagnostic rate was 66.7% and the most common clinical stage was stage I (7/9). All patients received surgical treatment and seven had postoperative chemotherapy, radiotherapy or hormone therapy. Conservation of unilateral ovary or bilateral ovaries was performed in 5 cases. Three patients underwent local excision, which resulted in the preservation of reproductive function. During the follow-up, 2 cases of uterine endometrial adenosarcoma recurred. One patient of clinical stage III containing sarcomatous overgrowth died from recurrence 13 months after surgery. The other one recurred 2 years after local excision of the tumor in the uterine cavity and she remained healthy since hysterectomy.</p><p><b>CONCLUSION</b>Uterine mullerian adenosarcoma is a rare tumor without specific clinical symptoms and signs. The diagnosis depends on pathomorphologic examination. The tumors show low malignant potential and the vast majority are at early stage. Surgical excision is the main treatment strategy with a good prognosis in the early stage disease with complete removal of tumors. The prognosis is poor in advanced adenosarcoma with sarcomatous overgrowth. Due to the relatively high rate of recurrence, long-term follow-up is recommended.</p>

Seven cases of epithelial ovarian carcinoma with brain metastasis / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To summarize the clinical characteristics, treatment, and prognosis of brain metastasis in patients with epithelial ovarian carcinoma.</p><p><b>METHODS</b>Retrospective analysis was conducted in 7 cases of brain metastases of epithelial ovarian carcinoma from January 1986 to March 2007 in Peking Union Medical College Hospital for summarizing therapy results and prognosis-affecting factors.</p><p><b>RESULTS</b>Incidence of brain metastases of epithelial ovarian carcinoma was about 0.66% (7/1055). Serous adenocarcinoma was the predominant pathological type in 4 cases and the subsequent was adenocarcinoma in 3 cases. All the patients were diagnosed at late stage, 6 cases with the International Federation of Gynecology and Obstetrics (FIGO) stage IIIc and 1 with FIGO stage IV. The mean duration from diagnosis of ovarian carcinoma to brain metastasis was 32.7 +/- 20.0 months (range, 23-73 months). Single metastasis focus occurred in 43% of cases and multiple metastases in 57% of cases. Fifty-seven percent of patients presented extracranial metastasis. Serum CA125 played a role in monitoring reoccurrence and brain metastases. The average survival time was about 12 months. Better treatment with prolonged survival could be achieved by combination of operation and chemotherapy or combination of radiotherapy with chemotherapy.</p><p><b>CONCLUSIONS</b>As a rare condition, brain metastasis of epithelial ovarian carcinoma is rising in incidence with improved treatment of ovarian carcinoma and prolonged survival. However, brain metastasis indicates bad prognosis which can be improved by combined therapy.</p>

Role of high-risk human papillomavirus testing in the screening and management of cervical cancer precursors / 中国医学科学院学报

Human papillomavirus (HPV) infection is an essential cause of cervical cancer. HPV testing therefore may maximize the clinical benefits of cervical screening and abnormal cervical cytology management. A negative HPV test in combination with a normal Pap test result in women age 30 years or older allows the safe extension of the cervical screening interval to 3 years. However, because HPV infection is common in young women and is usually transient, HPV testing is not recommended as part of primary cervical screening for women younger than 30 years. HPV testing is recommended for women of any age as a triage test with atypical squamous cells of undetermined significance (ASC-US) results and as an option for follow-up of women with HPV-positive ASC-US, atypical squamous cells "cannot rule out high-grade", low-grade squamous intraepithelial lesions, or atypical granular cells not found to have CIN 2/3. HPV testing is also recommended as an alternative to colposcopy and/or cytology for follow-up of treated cases. Proper use of HPV testing improves the management of women with cytologic abnormalities.

Comparison of three subcategories of laparoscopic hysterectomy / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the clinical characteristics of three subcategories of laparoscopic hysterectomy: total laparoscopic hysterectomy (TLH) and two subcategories of laparoscopic-assisted vaginal hysterectomy (LAVH): LAVHs and LAVHb.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 393 patients underwent laparoscopic hysterectomy, including TLH (n=178), LAVHa (n=177), and LAVHb (n=38), in our hospital from September 2002 to September 2005.</p><p><b>RESULTS</b>Myoma and adenomyosis of uterus were the most common diseases in this study, accounting for 66.9%, 38.4%, and 52.6% in TLH group, LAVHa group, and LAVHb group, respectively. The mean surgery duration and blood loss were not significantly different between TLH group and LAVHa group (P > 0.05), but were significantly less in TLH group than in LAVHb group (P < 0.05). The bulk of uterus in TLH group was significantly bigger than in other two groups (P < 0.05). The incidence of major complications in the TLH group (9. 0%) was lower than in LAVHa group (14.1%) and in LAVHb group (18.4%), but without statistical significance. Conclusion Compared with LAVH, TLH is feasible to deal with bigger uterus with less blood loss and shorter surgery duration and without more frequent complications.</p>

Phase II study of gemcitabine combined with platinum chemotherapy for recurrent epithelial ovarian cancer / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer.</p><p><b>METHODS</b>Phase II study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50.5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractory. All patients received gemcitabine combined with carboplatin or oxaliplatin chemotherapy. Patients' response rate (RR) and toxicity of gemcitabine combined with platinum chemotherapy were evaluated.</p><p><b>RESULTS</b>A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36.4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10.0 months (95% CI: 7.0-13.0) after initiation of gemcitabine combined with platinum chemotherapy. There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group (P = 0.061). Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8% of patients. Grade II/III anemia (54.5%) and grade III/IV neutropenia (54.5%) were most common toxicities. Ten (45.5%) patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen (63.6%) patients received granulocyte colony-stimulating factor to relieve neutropenia, and 8 (36.4%) patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treat-ment-associated death.</p><p><b>CONCLUSION</b>Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.</p>

Treatment options for patients with recurrent ovarian cancer: a review of 54 cases / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the efficacy of treatment options for patients with recurrent ovarian cancer.</p><p><b>METHODS</b>From 1990 to 2000, 54 patients with recurrent ovarian cancer primarily treated in Peking Union Medical College Hospital were selected and reviewed. All the clinical data related to the recurrent tumor were collected. Two-side P values for differences in survival were calculated by the Cox regression model.</p><p><b>RESULTS</b>The platinum-free interval > 6 months and the surgery followed by salvage chemotherapy prolonged survival time of the patients with recurrent ovarian cancer (95% CI = 0.153-0.987, P = 0.047; 95% CI = 1.611-10.914, P = 0.003, respectively). The increased number of chemotherapy cycles ( > 10 months) offered some benefit on the survival (95% CI = 0.110-1.090, P = 0.070). The initiation of treatment and chemotherapy regiments failed to demonstrate an improvement in survival.</p><p><b>CONCLUSION</b>The treatment options for patients with recurrent ovarian cancer depend on the platinum-free-interval of the patients. A strategy of secondary surgical cytoreduction followed by salvage chemotherapy is suggested for the patients with platinum-sensitive disease.</p>

Lymphadenectomy in the treatment of malignant ovarian germ cell tumor / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the impact of lymphadenectomy on the relapse and survival of malignant ovarian germ cell tumor (OGCT).</p><p><b>METHODS</b>The clinical data of 102 OGCT cases treated in Peking Union Medical College Hospital from June 1980 to June 2003 were analyzed retrospectively. All the data about lymphadenectomy during primary and secondary surgery were collected, and other factors related to prognosis were also collected at the same time. Chi-squared test was applied in the univariate analysis related to relapse of disease. Cox model was applied in multivariate analysis related to relapse and survival of disease.</p><p><b>RESULTS</b>Pelvic and paraaortic lymph node metastasis was not significantly related to prognosis in primary and secondary treated patients. Lymphadenectomy showed no significant impact on disease relapse and survival. In the primary treatment, International Federation of Gynecology and Obstetrics (FIGO) staging, chemotherapy regimen, residual tumor and lymphadenectomy were the significant factors related to the relapse. After being stratified for the chemotherapy regimen, lymphadenectomy was not significantly related to the relapse in bleomycin +etoposide +cisplatin or cisplatin +vincristine +bleomycin regimen group, and lymphadenectomy could prevent relapse in no chemotherapy or other chemotherapy regimen group. In relapsed patients, only residual tumor was significantly related to survival time after relapse.</p><p><b>CONCLUSIONS</b>Pelvic lymph node metastasis is not the significant risk factor related to prognosis. Lymphadenectomy may have a beneficial effect on survival, although such effect is not significant. Although lymphadenectomy provides important information for prognosis, they provide little benefit to those patients already requiring chemotherapy based on the original operative findings. Lymphadenectomy should be performed to primary or relapsed patients by an expert surgical team.</p>

Clinical features and treatment of cervical malignant tumor in young women / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate clinical characteristics, prognosis, prognostic factors, and the ideal treatment of the young patients with cervical malignant tumor.</p><p><b>METHODS</b>We analyzed retrospectively 52 cervical malignant tumor patients younger than 35 years (study group) and 45 cervical carcinoma patients older than 50 years (control group) who were admitted in Peking Union Medical College Hospital from 1985 to 2002. The data were analyzed statistically by SPSS10.0. The ovarian functions were evaluated by the questionnaire and the serum sex hormone assay.</p><p><b>RESULTS</b>In study group, the median age was (31.0 +/- 0.6) years old. The most common clinical symptoms were contact bleeding and irregular bleeding; 55.8% of patients had more than one symptom. HPV positive rate was 20.5%, which was higher than control group significantly (P < 0.05). The percentage of advanced stage (stage II b-stage IV b) of disease in study group and control group were 30.8% and 22.2%, respectively, the difference was significant (P < 0.05). The most common histological type was squamous cell carcinoma (71.2%) in study group, while the percentage of non-squamous cell carcinoma (43.8%) in patients younger than 30 years was much higher than control group (P < 0.05). All the histological type was non-squamous cell carcinoma in the patients younger than 25 years. Histological grade showed that G1, G2, and G3 were 21.2%, 54.5%, and 24.2% respectively in study group. The percentage of bulky cervix (tumor diameter > 4 cm) in study group and control group was 27.9% and 2.7% respectively (P < 0.005). The overall 5-year survival rates were 75.7% in study group, lower than control group (P < 0.05). The COX hazards regression model showed histological type (P = 0.003) and bulky cervix (P = 0.001) were of significant prognostic values.</p><p><b>CONCLUSIONS</b>There are more advanced stage carcinoma and non-squamous cell carcinoma patients with poor prognosis in study group. The treatment to younger patients should be concerned individually, as well as preservation of reproductive and female endocrine function should be considered.</p>

Internal Ribosomal Entry Site-Mediated Expression of Human Multidrug Resistance 1 Gene in Human CD34(+) Cells / 中国实验血液学杂志

In order to reach the purpose of co-transferring double drug resistance genes into human CD34(+) progenitor cells to broaden the spectrum of drug resistance, the expression efficiency of human multidrug resistance 1 (MDR1) gene mediated by the internal ribosomal entry site (IRES) was investigated. Two retroviral vectors were transferred into packaging cells. One is pSF-DIM containing double drug resistance genes, in which the translation of MDR1 gene was controlled under an IRES from encephalomyocarditis virus. The other is pSF-MDR1 which only contains MDR1 gene controlled under the same promoter of pSF-DIM. The amphotropic retroviral packaging cells PA317/pSF-DIM and PA317/pSF-MDR1 were obtained with titer of 8 x 10(4) and 1.3 x 10(5) cfu/ml respectively. Human cord blood CD34(+) cells were transduced by supernatant infection. Expression of P-gp was detected by flow cytometry. Compared with the untransduced group, the expression of P-gp in pSF-DIM transduced group and pSF-MDR1 transduced group was elevated 10.92% and 28.82% respectively. However, the expression of P-gp in pSF-MDR1 transduced group was higher than that in pSF-DIM transduced group. The result suggests that MDR1 gene can express in the human progenitor cells under control of IRES. It laid the foundation of subsequence research. The reason on the difference in MDR1 gene expression efficiency between pSF-MDR1 transduced group and pSF-DIM transduced group need further research.

Clinical analysis of the effect of cervical conization on fertility and pregnancy outcome / 中华妇产科杂志

0.05).Among the 26 pregnancies,there occurred one ectopic pregnancy and four cases of spontaneous abortion.In the 13 delivery cases,there were one premature delivery,two cases of premature rupture of the membrane,and ten cases of cesarean section.The sample height of the cone was less than 2.0 cm in the nine delivery cases,and the mean width of the cone was over 2.5 cm.Conclusion No evidence of secondary infertility caused by cervical conization was found.There was also no significant increase in the number of either premature delivery cases or low birth weight infants. The sample height of the cone might play a more important role in the pregnancy outcome than the width, which still needs to be further verified by larger studies.

Evaluation of the follow up results of patients with cervical intraepithelial neoplasia Ⅲ after surgical treatment / 中华妇产科杂志

Objective To evaluate the follow-up results of patients with cervical intraepithelial neoplasia Ⅲ(CIN Ⅲ)after surgical treatment.Methods A retrospective analysis of consecutive patients with CIN Ⅲ after surgical treatment between Jan 1st,1999 and Jun 30 th,2004 was performed.The follow- ups of the patients after surgical treatment were assessed.Results In the follow-up of patients with CINⅢ after surgical treatment,the rate of abnormal cytology was 9.3%.The rate of follow-up was higher in patients with cervical conization than in patients with initial hysterectomy and in patients of the oncological group than of the non-oncological group.The rate of follow-up was lower in patients over 40 years old.There was no difference in the residential areas of the patients.Conclusions Cytological follow-up of patients with CINⅢ after operation is varied.The rate of follow-up is lower in patients over 40 years old,in patients having initial hysterectomy and in patients of the non-oncological group.The rate of follow-up is associated with the knowledge about CIN of both surgeons and patients.

Proteomic analysis of human ovarian cancer cell lines and their platinum-resistant clones / 中华妇产科杂志

Objective To perform comparative proteomic analysis of human ovarian cancer cell lines for detecting platinum-resistance associated proteins.Methods The total proteins of two sensitive (SKOV3 and A2780)and four resistant(SKOV3/CDDP,SKOV3/CBP,A2780/CDDP and A2780/CBP) human ovarian cancer cell lines were separated by two-dimensional gel electrophoresis(2-DE).The differentially expressed proteins were analyzed using image analysis software,stained with Coomassie Brilliant Blue,then identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS)and database searching.The mRNA and protein levels of the differentially expressed protein which was most significant in all of the four resistant cell lines were validated by RT-PCR and western blotting,respectively.Results Five proteins were found to be significant in four cell lines. Annexin A3 and destrin were up-regulated and nicotinamide-adenine dinucleotide phosphate(NADP)- dependent isocitrate dehydrogenase 1 was down-regulated in all the four resistant samples.Glutathione transferase omega 1 had an increased expression in the other three resistant cell lines except for SKOV3/CBP in which its expression was not changed.However,cofilin 1 represented a different trend.In the two resistant sublines of SKOV3,eofilin 1 had a down-regulation,but it had an up-regulation in the cell lines induced from SKOV3.The expression of annexin A3 was up-regulated by 3-20 fold and the results of RT- PCR and western blotting showed complete consistency with that by 2-DE.Conclusions Proteomic techniques are useful to the identification of the resistance-associated proteins in ovarian cancer platinum- resistant cell lines and five candidates have been found.The five differential proteins might become hopeful candidate biomarkers for resistance.